Solid phase preparation of amines

Abstract

A method for the solid phase preparation of an amine by a novel synthesis is described where a diol is monoalkylated with a chloromethyl resin followed by reaction with N,N'-carbonyldimidazole to afford a resin-bound tertiary-alkoxycarbonyl-imidazole which is subsequently N-alkylated and then sequentially treated with appropriate building blocks and reagents to afford a resin-bound amine which affords the desired amine after treatment with an acid as well as other valuable intermediates used in the process.

We claim: 
     
       1. A method for the synthesis of an amine which comprises: Step (a) treating a compound of Formula 2 ##STR25##  wherein n is an integer of 2 to 5 with a resin of Formula 3 ##STR26##  wherein P is a styrene/divinylbenzene copolymer in the presence of a base and solvent to afford a compound of Formula 4 ##STR27##  wherein P and n are as defined above; Step (b) treating a compound of Formula 4 with 1,1'-carbonyldiimidazole in the presence of a base and a solvent to afford a compound of Formula 5 ##STR28##  wherein P and n are as defined above; Step (c) treating a compound of Formula 5 sequentially with methyl trifluoromethanesulfonate (MeOTf) and a tertiary amine base in a solvent to afford in situ a compound of Formula 6 ##STR29##  wherein P and n are as defined above; Step (d) sequentially adding the appropriate building blocks and carrying out the appropriate reactions to synthesize an carbamate of Formula 8 ##STR30##  wherein P and n are as defined above; Step (e) treating a compound of Formula 8 with an acid in a solvent to afford an amine.   
     
     
       2. A method according to claim 1 wherein the resin of Formula 3 is Merrifield resin. 
     
     
       3. A method according to claim 1 wherein the base in Step (a) is potassium tertiary butoxide. 
     
     
       4. A method according to claim 1 wherein the solvent in Step (a) is tetrahydrofuran. 
     
     
       5. A method according to claim 1 wherein the base in Step (b) is 4-dimethylaminopyridine. 
     
     
       6. A method according to claim 1 wherein the solvent in Step (b) is dimethylformamide. 
     
     
       7. A method according to claim 1 wherein the base in Step (c) is triethylamine. 
     
     
       8. A method according to claim 1 wherein the solvent in Step (c) is 1,2-dichloroethane. 
     
     
       9. A method according to claim 1 wherein the acid in Step (e) is trifluoroacetic acid. 
     
     
       10. A method according to claim 1 wherein the solvent in Step (e) is dichloromethane.